Combinations of peroxide lipids and organosilicon compounds, cosmetic and dermatological compositions containing same, and uses thereof, in particular for treating alopecia

ABSTRACT

PCT No. PCT/FR97/00141 Sec. 371 Date Jul. 24, 1998 Sec. 102(e) Date Jul. 24, 1998 PCT Filed Jan. 24, 1997 PCT Pub. No. WO97/26892 PCT Pub. Date Jul. 31, 1997Combinations, in particular for use as the active principle in a cosmetic or pharmaceutical and particularly dermatological composition, containing 1-6 parts by weight of peroxidised lipids per 0.01-0.1 parts by weight, based on the organic silicon, of a biologically active organosilicon derivative, are disclosed. Cosmetic or dermatological compositions containing such combinations are also disclosed. Said compositions are particularly useful for treating alopecia.

The present invention relates to novel combinations of peroxidisedlipids and organosilicon compounds, cosmetic and dermatologicalcompositions containing them, as well as to their applications,especially for the treatment of alopecia.

Hair loss, also known as alopecia, is a problem which is mostparticularly spread over the whole of the population, especially in themale population but also in the female population.

Many studies have been dedicated to this problem. As regards femalealopeciae disseminatae, the development on female alopeciaedisseminatae, carried out by P. Reygagne, and which appear in bedc,1993, 1, 7, 327-338, may be cited in particular. In this study, itemerges that alopeciae disseminatae are currently the subject of threetypes of treatment:

general treatments, such as the combination of vitamin B5 and vitamin Hor vitamin B8,

minoxidil prescribed locally which causes a moderate re-growth in 30% ofcases, but the positive effect of which ceases to manifest itself in the3 to 6 months following the stopping of the applications,

endocrinological treatments in cases of androgenetic alopeciae.

In general, androgenetic alopecia is the most frequent of alopeciae and,without doubt, that for which the therapeutic demand is the highest.However, the anti-androgenetic treatments per os which have a certaineffectiveness in the woman are not practical in the man and no localanti-androgenetic treatment has found long-lasting effectiveness. Theonly local treatment being able to demonstrate in several controlledstudies a certain effectiveness in the man is minoxidil in atwice-weekly local application. The first studies made between 1982 and1986 were relatively optimistic with 18 to 53% re-growth. Such a studyis given in: Androgenic alopecia: clinical aspects and treatment, in"Hair and Hair Diseases" C. E. ORPHANOS, R HAPPLE (Eds),Springer-Verlag, Berlin Heidelberg 1990, PP 485-527. Cosmeticallyacceptable re-growths are in fact rare, as related by RUSHTON D. H.,VUGER W. P., COTTERIL P. C., KINGSLEY P., JAMES K. C. in "Quantitativeassessment of 2% topical Minoxidil in the treatment of male patternbaldness", Clin Exp Dermatol, 1989, 14, 40-6. Moreover, OLSEN E. A.,WEINER M. S. AMARA I. A., DELONG E. R., have indicated in the articleentitled "Five-year follow-up of men with androgenetic alopecia treatedwith topical Minoxidil" in J. Am Acad Dermatol 1990, 22, 643-6, a slowreturn of the hair loss after 1 year of treatment, even if the treatmentis continued. Furthermore, a systemic diffusion limits the increase inthe local concentration of minoxidil and the preparations currentlymarketed are all dosed at 2% minoxidil.

Various peroxidised lipids are known, which are notably obtained by aperoxidation of natural vegetable oil. The following patents shall becited in particular: BSM N°2 330 M, EP-A-293 535, FR-A-2 591 112,EP-A-225 831, EP-A-225 832, EP-A-225 833, EP-A-226 506, FR-A-2 461 744,FR-A-2 539 142 and EP-A-117 962, which relate either to the preparationof such peroxidised lipids, or to their applications in various fields,particularly in the treatment of certain illnesses in the field ofrheumatology or traumatology, or even as a healing product.

Peroxidised lipids of this type have also been used according toEuropean patent EP-A-0 480 983 for the treatment of circulatoryinsufficiencies by local application.

Many references are found in the literature which relate to the activityof organic silicon on the stimulation of the biosynthesis of collagen orof elastin, in the reconstitution of the damaged connective tissue. Itemerges from the experimental works given in the various publications,that in particular, the organic silicon causes a return to a normallevel of the arterial wall degraded by the attack of an artificiallycaused atheroma.

More specifically, in J. Med. Esth and Chir. Derm., volume XII, 47,September 1985, pages 187-190, F. MARCHI-LIPSKI and F. DANIEL havecarried out a bibliographical analysis concerning the therapeuticinterest of silicon in the ageing of connective tissue. It emerges fromthis study that silicon has a most particular importance in the upkeepof the integrity of connective tissue and that the organosiliconderivatives enable efficiently fighting against the ageing of connectivetissue in all its forms.

It also emerges from this article that there exists soluble organicsilicon derivatives which can be used according to variousadministration routes and notably by local application.

Amongst the many therapeutic applications cited in this article, theapplication for improving the growth and the density of the hair israised.

In the chapter dedicated to the biological activity of silatranes inTopics in Current Chemistry, vol. 84, pages 77-135, 1979, Michail G.Voronkov has demonstrated the importance of these silatranes in thetreatment of alopecia.

Furthermore, the French patent FR-2,645,863 described silicon compoundsin the form of molecular complexes of a silanol which are prepared bythe reaction of an alkaline salt or ammonium salt of a silanol with anacid in the presence of a zeolite. These silanol complexes may, interalia, be used for improving the re-growth of hair.

It is this type of complex which is used for the preparation of theproduct sold under the commercial trade name M 44 by LaboratoiresCARILENE.

Such a product for stopping hair loss acts, due to the presence oforganic silicon, as:

a tonic for the vascular walls, which leads to the improvement of thepapillary vascularization,

a regulator of cell metabolism which favours the anagenic phase of thepilary cycle,

a stimulant of the synthesis of collagen and of elastin which enablesthe restructuration of the pilary stem,

a sebo-regulator, which leads to the decrease in the excess of sebum.

Pursuing his research with the view to improving the performances of theproducts for treating alopecia, the inventor of the present inventionhas noticed that combinations of peroxidised lipids and organic siliconderivatives, in particular silanol derivatives led to a considerableincrease in the activities of the two products, enabling perfectlyunexpected performances in the treatment of alopecia, in particularalopecia of the androgenetic type.

These combinations do in fact allow obtaining results at leastequivalent to those obtained with minoxidil as well as preventing thedrawbacks of the latter product, namely the lack of remanance of theobserved effect once the treatment is stopped. Furthermore, anothernon-negligible advantage of these combinations with the respect tominoxidil is that they cause no increase in seborrhoea during treatmentand necessitate only one application per day and not two.

A randomised controlled study of the effectiveness of these combinationshas enabled demonstrating, without ambiguity, the effectiveness of thesecombinations. The effectiveness of these combinations was compared tothat of minoxidil, the only current reference product in the treatmentof androgenetic alopecia. The experimental method for making thiscomparison was that of phototrichograms, the only method recognisedtoday as being perfectly reliable. The protocol and the results of thisstudy are given in the examples of the present text.

Hence, according to a first aspect, the invention relates, as novelindustrial product, to combinations of the two types of chemicalproducts, namely peroxidised oils and organic silicon compounds, inparticular silanol derivatives.

According to a second aspect, the invention also relates to cosmeticcompositions as well as to pharmaceutical compositions, notablydermatological compositions, which contain these combinations as activeprinciple.

According to another of its essential aspects, the invention alsorelates to the use of these combinations and compositions in thetreatment of alopecia.

According to another aspect, the invention relates to other applicationsof these combinations and compositions in which the same effect ofpotentiation of the effect of one of the two active substances by theother has been observed. In particular, this is what is observed for thetreatment of the effects of ageing of the skin, healing and tissueregeneration, as well as in the treatment of cellulite.

More specifically, according to one of its essential characteristics,the invention relates to a combination, notably useful as the activeprinciple in a cosmetic or pharmaceutical composition, notablydermatological composition, characterised in that it contains 1 to 6parts by weight of peroxidised lipids per 0.01 to 0.1 part by weightbased on the organic silicon of a biologically active organosiliconcompound.

According to a particularly advantageous embodiment, these combinationsare in the form of stable emulsions.

The peroxidised lipids, which can be used in accordance with theinvention, may be of very varied chemical nature but advantageously havea peroxidation rate between 30 and 500 milli-equivalents per kilo,preferably between 50 and 300 milli-equivalents per kilo, preferablystill between 50 and 150 milli-equivalents per kilo.

According to a particular embodiment, these lipids advantageously have aglyceride oxides content between 5 and 40%.

In accordance with the invention, at least one peroxide obtained byperoxidation of lipids of plant origin, for example in the form of atleast one natural vegetable oil, is preferably used as peroxidisedlipids. Preferably, these oils are selected from sweet almond oil,hazelnut oil, peanut oil, maize oil, grape seed oil, sesame oil and oilof safflower.

According to a particular embodiment of the invention, peroxidisedlipids are used, which are principally or mainly constituted oftriglycerides of the general formula: ##STR1## in which the radicals Rare mainly represented by the peroxidised octadecanoic and octdecanoicacids.

The biologically active organosilicon derivatives, which are usefulaccording to the invention, can be any water-soluble organic siliconderivative and which is known for its biological activity.

These may be free or condensed soluble organosilanol, organosilanediolor organosilanetriol derivatives. These soluble derivatives areadvantageously in the form of salts or complexes of the correspondingorganosilanols, referred to hereinafter as silanol as a means ofsimplification.

These derivatives will advantageously be selected from solubleorganosilanol derivatives of formula [R_(n) Si(OH)_(4-n) ]x, in whichO<x≦4, the n groups R are identical or different and representindependently hydrogen or an alkyl or aralkyl group and n is between 1and 3.

The nature of the various R groups is such that said organosilanolscorrespond to soluble and non-toxic derivatives.

As examples of such soluble silanols derivatives, the following may becited: potassium monomethylsilanetriol, perhydrolyseddimethylsilisalycilate, monomethylsilanetriol mannuronate,dimethylsilanol hyaluronate, ascorbyl methylsilanol pectinate,methylsilanol aspartate hydroxyprolinate.

In general, any organosilanol which is soluble in water, and thereforebiologically active and assimilated, can be used as silanol derivative.

As other examples of silanol derivatives which can be used to preparethe combinations useful according to the invention, silicon compoundscan also be cited, which are described in the French patent FR-2,645,863given here by reference. More specifically, these silicon compounds arein the form of a molecular complex of a silanol of general formula##STR2## wherein R is an alkyl or aryl group and R' and R" are alkyl,aryl or OH groups, and an alkaline or ammonium derivative of an acid.

Such products are obtained in particular from an alkaline salt or anammonium salt of a silanol, which is combined with an acid in thepresence of a zeolite which allows complete reaction of the twoproducts.

As emerges clearly from the following examples, the interest of thecombinations according to the invention is that they can be used asactive principle in cosmetic or pharmaceutical compositions, notablydermatological compositions, by conferring to these compositions notonly the combined advantages of the two types of active principles ofwhich they are comprised, but also a true synergy of these activities.

This synergy proves to be particularly interesting in the case of thetreatment of alopecia, in particular androgenetic alopecia.

The combinations of the invention enable, due to the presence ofoxidised glycerol triesters, to act upon the almost immediatere-establishment of the arterial blood flow within the pilary follicle,consequently, to cause a rush of blood which can rapidly act upon thestopping of an excessive hair loss, and can even eventually permit there-growth of the vellus.

Concurrently to this action, the soluble organic silicon contained inthe combination intervenes both to vehicle the first active principleand to render the damaged arteries of the follicle their motor function,which assures an upkeep in the long term of the normal blood flow, evenafter the stopping of the treatment, by the virtue of the regenerationof the arterial connective tissue.

Thus, a synergy of the two therapeutic activities is created which islinked to the action of blood flow accelerator and to the healing actionby activation of the cellular renewal due to the presence of oxidisedglycerol triesters, and to the action of catalyst of the biosynthesis ofthe connective tissue due to the presence of the silicon derivative,which lead to the restructuration of the walls of veins, arteries andcapillaries.

The two active principles which constitute the combinations of theinvention have therefore a conjugated action, which leads to a greaterirrigation in the pilary follicle at the same time as to a regenerationof hair-nourishing system.

Hence, according to one of its essential aspects, the present inventionrelates to cosmetic or pharmaceutical compositions, notablydermatological compositions, which contain as active principle acombination as described above.

These compositions advantageously contain from 1 to 6% by weight ofperoxidised lipids and from 0.01 to 0.1% by weight, based on the organicsilicon, of a biologically active organosilicon derivative, inparticular a soluble silanol derivative, and a cosmetically orpharmaceutically acceptable vehicle.

These compositions can be used in any field in which a potentiation ofthe activity of the peroxidised lipids by that of the siliconderivatives is sought.

This effect has been particularly observed in the case of the treatmentof alopecia, in particular androgenetic alopecia, as emerges from theexamples.

However, the interest of the combinations is not limited to this type oftreatment since they may be used in any type of cosmetic orpharmaceutical treatment, notably dermatological treatment, in which itis sought to treat or to look after the skin, the scalp or the hair, inparticular with the view to fighting against the effects of ageing, forimproving healing and tissue regeneration as well as for fightingagainst hair loss and for improving hair re-growth.

According to these methods, a cosmetically or pharmaceutically activeamount of a composition such as described above is applied onto the partof the body to be treated.

Consequently, if the combinations according to the invention prove to beparticularly effective for the preparation of pharmaceuticalcompositions, notably dermatological compositions, for application ontothe scalp and/or the hair with the view of treating alopecia, notablyandrogenetic alopecia, the combinations also prove to be very useful indifferent treatments, such as the treatment of cellulite, the upkeep orthe treatment of the hair with the view of fighting against its ageing,as well as any treatment for improving the healing or the regenerationof tissues.

The compositions according to the invention may be in any galenic formwhich can be used in function of the effect sought after and of the areaof the body to be treated. These compositions may be lotions, gels,creams, shampoos, these galenic forms being intended for the scalp orthe application onto the face or the body.

The following examples are given purely as an illustration of theinvention.

EXAMPLES

Unless otherwise indicated, the concentrations in the Examples below aregiven in percentages by weight.

Example 1

    ______________________________________                                        Formula of a cream for care of the body or the face.                          ______________________________________                                        Oxidised glycerol triesters                                                                           10                                                      Potassium monomethylsilanetriol 0.5                                           Excipients, preservatives, perfumes  qs 100                                 ______________________________________                                    

This cream is applied by light massage once or twice a day in atreatment of 3 months minimum.

This cream is particularly useful for improving the cell renewal, forfighting against cellulite and stretch marks. Furthermore, it improveshealing and acts as an anti-inflammatory and has an analgesic andsoothing effect.

Example 2

    ______________________________________                                        Formula of a lotion for care of the body or the face                          ______________________________________                                        Oxidised glycerol triesters                                                                             3                                                     Potassium monomethylsilanetriol 0.1                                           Cosmetic alcohol 99°  15                                               Permutated water, perfumes, preservatives,  qs 100                          ______________________________________                                    

This lotion is applied with the aid of cotton wool at the rate of a fewdrops of lotion, in the evening, on the body or the face. Theapplication is renewed for a minimum of 3 months.

This lotion is particularly useful for improving cell renewal, forfighting against cellulite and stretch marks. Furthermore, it improvesthe healing and acts as an anti-inflammatory and has an analgesic andsoothing effect.

Example 3

    ______________________________________                                        Hair lotion                                                                     A composition having the composition below, in percentages by                 weight, is prepared:                                                        ______________________________________                                        Potassium monomethylsilanetriol citrate                                                                1                                                      Protein hydrolysate 0.5                                                       Keratin hydrolysate 0.5                                                       Amino acid complex 0.1                                                        Peroxidised maize oil (Epaline 100 ®) 3                                   Absolute alcohol for cosmetology 10                                           Gardienia essence 0.05                                                        Excipient, preservative and demineralised water  qs 100                     ______________________________________                                    

This lotion is applied onto the scalp, part by part, at the rate of afew drops, preferably in the evening. The application is renewed for 3months minimum.

Example 4

Clinical test of effectiveness against alopecia.

The effectiveness of the composition of Example 3 against hair loss andseborrhoea was tested, in comparison with minoxidil on a population of60 men of 18 to 65 years old suffering full androgenetic alopecia,having an alopecia of the androgenetic type at stage III to VI accordingto the Hamilton classification.

The comparative test was carried out under the following conditions overa period of 9 months. The patients were grouped into two homogeneousgroups of the same importance.

a) Protocol of the test

a-1: Initial evaluation

Each patient was subjected to an initial assessment (at D0) whichcomprises:

1--Measuring of the diameter of the area of alopecia on the top of thehead.

2--Filling-in a questionnaire.

3--Carrying out a pre-therapeutic phototrichogram:

This necessitates in the first instance the shaving and thesemi-permanent tattooing of the area to be photographed. This tattoo isdone with the aid of disposable sterile needles having three branches.The area is selected in front of the vertex in an alopecic area having apercentage of telogenic hair which is a priori greater than 20%. On asurface of about 2 cm², the hair is cut short on D0 with the aid ofcurved scissors. Two semi-permanent tattoo points then allow marking outan imaginary square of 7×7 mm within which the hairs will be counted.These two tattoo points will correspond to two fixed marks on theviewing system. It is necessary to be aware that the hair will all havethe same parallel orientation in the interior of the imaginary square of7×7 mm.

After this operation, a macrophotograph is taken on D0 understandardised and perfectly reproducible conditions of distance, lightingand enlargement (×3). A second comparative photograph is taken on D0+2days. The comparison of the two photographs enables differentiating thehairs in anagenic phase which have grown, and hairs in telogenic phase,which have not grown.

This technique therefore enables studying

the density of hairs per cm²,

the number of anagenic hairs (A),

the number of telogenic hairs (T),

the ratio A/T,

the percentage of anagenic hairs (A %),

the speed of hair growth,

their diameter (D).

The phototrichogram is repeated after three months from the first periodof treatment (M₃), a third time three months later, upon the completionof the second period of treatment (M₆).

4--Sampling of the hair

A bunch of hair is taken from the area to be shaven for thephototrichogram. This bunch shall be linked to the base, stored in anumbered tube, and allows measuring of the diameters of the hair lateron.

a-2. Treatment

After taking the first phototrichogram, each patient is given a boxcontaining the three first months of treatment (13 weeks). These boxesare numbered from 1 to 60, and the numbers are attributed to eachpatient according to the order of his arrival in the study. Each boxcontains either three flasks of minoxidil, or three flasks of lotion ofexample 3. Each flask of minoxidil and each flask of lotion according tothe invention has on it a sticky label bearing the number of the box towhich it belongs.

The test being randomised, the numbers of the boxes (30 boxes ofminoxidil and 30 boxes of lotion of example 3) are attributed by virtueof a randomisable table which is equilibrated every four patients.During the period of treatment of 13 weeks, each patient uses either 1ml of minoxidil applied locally every day, morning and evening, or 3 mlof lotion of example 3 applied locally once a day in the evening.

At the end of the first period of treatment (noted time M3), after thesecond monitoring visit and the preparation of this secondphototrichogram, a second numbered box of treatment was given to eachpatient. This box contains either the product of example 3, orminoxidil. The second period of treatment lasts also for three months(13 weeks). At the end of this period (noted time M6), a thirdphototrichogram is made. Finally, a fourth phototrichogram was made onthe different patients after the complete stopping of the treatment for13 weeks (noted time M9).

During these treatments, the following treatments are authorised:

shampoos: free. The patients may wash their hair every day if they wish,with the shampoo of their choice. The best is that they pursue theirnormal shampooing if this is convenient to them.

Colouring, bleaching and perms: these are authorised. It is simplynecessary to avoid that they are not done during the period of thepreparation of phototrichograms.

In contrast, the following are not authorised:

Any local or general treatment which may have an effect upon the growthor of the loss of the hair is forbidden throughout the study, and duringthe three months preceding the inclusion. Particularly forbidden are:prostaglandins, rubefacients, any vasodilator, any anti-androgen, andany local hormonal treatments.

b) Results

The study showed, for the anagenic hair counts, telogenic hair counts,and total hair counts, as well as the anagenic/telogenic ratios of themonths M₀ and M₆, an equivalence between the two products since the veryslight differences that may be noticed, of which certain are in favourof the product of example 3, are not statistically significant.

The clinical projection of these counts leads the clinician to concludea real anti-hair loss activity of the two products as well as a certainactivity upon the re-growth.

The statistical study led from the results of the phototrichograms leadsconcluding the equivalence between the two products tested as regardsthe anagenic (A) over telogenic (T) ratios. These results are clearlygiven in table 1 below:

                  TABLE 1                                                         ______________________________________                                        Evolution of the ratio between M6 and M0                                                       Treatment group                                                             Lotion of                                                        example 3 Minoxidil Total                                                   ______________________________________                                        Difference N         32.00      28.00  60.00                                    M6/M0:A/T Missing data 1.00 0.00 1.00                                          Average 0.0 -0.5 -0.2                                                         Standard 2.3 2.9 2.6                                                          deviation                                                                     Minimum -4.75 -9.13 -9.13                                                     Maximum 7.33 6.14 7.33                                                     ______________________________________                                    

wherein it appears that no difference was detected between the twotreatment groups as regards the evolution of the ratio of the number ofanagenic hairs over the number of telogenic hairs between M6 and M0.

Furthermore, no significant difference was detected for this sameevolution between M3 and M0 (p=0.057).

Furthermore, table 2 below shows that no difference was observed for thetwo products as regards the difference in the percentages of anagenichairs between M6 and M0.

                  TABLE 2                                                         ______________________________________                                        Percentage of anagenic hair:-difference M6-M0                                                 Treatment group                                                             Lotion of                                                         example 3 Minoxidil Total                                                   ______________________________________                                        Difference                                                                              N         32.00      28.00  60.00                                     M6/M0:% Missing data 1.00 0.00 1.00                                           Anagenics Average -0.4 -3.2 -1.7                                               Standard 11.0 12.8 11.9                                                       deviation                                                                     Minimum -32.54 -39.80 -39.80                                                  Maximum 23.66 22.40 23.66                                                  ______________________________________                                    

Furthermore, no difference was detected between the two groups oftreatment between M3 and M0.

In contrast however, the table 3 below shows that the total number ofhairs in the marks depends upon the treatment followed.

                  TABLE 3                                                         ______________________________________                                        Total number of the hair in the marks-difference M6-0                                         Treatment group                                                             Lotion of                                                         example 3 Minoxidil Total                                                   ______________________________________                                        Difference                                                                             N          32.00     28.00   60.00                                     M6/M0:Total Missing data 1.00 0.00 1.00                                        Average -2.9 6.4 1.4                                                          Standard 9.4 9.4 10.5                                                         deviation                                                                     Minimum -22.00 -18.00 -22.00                                                  Maximum 22.00 28.00 28.00                                                  ______________________________________                                    

A significant difference (p<0.001) was detected between the two groupsof treatment as regards the evolution of the total number of the hairsin the marks between M6 and M0.

As an indication, there was also a significant difference (p=0.001)between M3 and M0. This difference may be explained by the increase ofthe number of telogenic hairs in the minoxidil group. It is to be notedthat this type of hair (telogenic) is led to fall in the three months.

A very clear difference is also observed as regards the number oftelogenic hairs after 6 months of treatment. This difference is clearlyseen in table 4 below.

                  TABLE 4                                                         ______________________________________                                        Number of telogenic hairs-difference M6-M0                                                    Treatment group                                                             Lotion of                                                         example 3 Minoxidil Total                                                   ______________________________________                                        Difference                                                                              N         32.00      28.00  60.00                                     M6/M0:T Missing data 1.00 0.00 1.00                                            Average -0.8 3.4 1.2                                                          Standard 6.2 8.1 7.4                                                          deviation                                                                     Minimum -16.00 -12.00 -16.00                                                  Maximum 10.00 29.00 29.00                                                  ______________________________________                                    

A significant difference (p=0.025) was detected between the two groupsof treatment as regards the evolution of the number of telogenic hairsbetween M6 and M0.

As an indication, there was no difference for this evolution between M3and M0.

From the results of this statistical study given in the tables above, itnevertheless emerges a better quality of hair after treatment for 6months with the lotion of the invention with the respect of thatobserved after treatment with minoxidil since, even if minoxidil furtherfavours the re-growth of the hair, the telogenic hairs are found in ahigher percentage.

From a clinical point of view, the important improvement brought aboutby the product of example 3, in comparison with minoxidil, must be takeninto account:

One sole application per day (instead of 2)

A non-greasy product, which did not necessitate shampooing after use,

Absence of seborrhoea (minoxidil stimulates the production of sebum bythe sebaccic glands)

A hair whose diameter has increased with respect to the minoxidil group

An overall approach of the results to M6 has led the clinician toindicate a long term action, which must permit the stopping of thetreatment once good results are obtained, whereas minoxidil necessitatesa life-time treatment, since the upkeep of the results obtained islinked to an uninterrupted use. This "slow-release" treatment wasconfirmed by results at M9

A low percentage of alcohol.

The results of this comparative study over 9 months indicate in table 5below as regards the reference product minoxidil for a twice-weeklyapplication of the product during the first six months of the study, andin table 6 below for the product of example 3, applied once daily,during the first six months of the treatment, the treatments beingstopped in both cases after six months.

                  TABLE 5                                                         ______________________________________                                        Reference product                                                                        M0     M3          M6   M9                                         ______________________________________                                        A          45.89  59.33       49.43                                                                              42.71                                        T 14.29 11.83 17.57 19.10                                                     A/T 3.21 5.01 2.82 2.23                                                       A% 76.55 83.93 74.03 69.49                                                    N* 61.40 70.77 67.00 61.81                                                    D (μm) 70.00 73.71 77.18 77.76                                           ______________________________________                                         N*:Number of hairs in the marks                                          

                  TABLE 6                                                         ______________________________________                                        Product of example 3                                                                     M0     M3          M6   M9                                         ______________________________________                                        A          47.24  51.45       46.73                                                                              44.65                                        T 15.64 12.21 13.23 15.96                                                     A/T 3.02 4.21 3.53 2.79                                                       A% 75.07 80.59 76.68 73.61                                                    N* 62.68 63.67 60.27 60.92                                                    D (μm) 74.85 79.68 80.31 80.27                                           ______________________________________                                    

The experimental protocol of the comparative clinical study withminoxidil allows prolonging the study for three months after thestopping of the treatment.

The growth parameters-anagenics, percentage of anagenics, number oftotal hair-remain with a remarkable stability in the group treated bythe product of example 3, against a rapid return to the pathology in thegroup treated by minoxidil.

Consequently, the therapeutic regimen recommended with the product ofexample 3 consists in taking advantage of this "slow-release" effect andin stipulating periods of stopping of treatment of three months, afterthe first three months of initial treatment. A treatment of three monthswill therefore be envisaged, followed by three months of stopping of thetreatment, and then a continuation of the treatment for three months,etc.

This obviously represents an important advantage for the use of theproduct in that it is quality of life or the price of treatment.

What is claimed is:
 1. A combination comprising 1 to 6 parts by weightof peroxidized lipids and 0.01 to 0.1 part by weight based on organicsilicon of a biologically active organosilicon compound.
 2. Thecombination according to claim 1, in the form of a stable emulsion. 3.The combination according to claim 1, wherein said peroxidized lipidshave a peroxidation rate between 30 and 500 milliequivalents per kilo.4. The combination according to claim 1, wherein said peroxidized lipidsare obtained by peroxidation of lipids of plant origin.
 5. Thecombination according to claim 4, wherein the lipids of plant origin areobtained from at least one natural vegetable oil selected from the groupconsisting of sweet almond oil, hazelnut oil, peanut oil, maize oil,grape seed oil, sesame oil and oil of safflower.
 6. The combinationaccording to claim 1, wherein the peroxidized lipids have a glycerideoxides content between 5 and 40%.
 7. The combination according to claim1, wherein said organosilicon compound is a water-soluble organosilanol,organosilanediol or organosilanetriol derivative.
 8. The combinationaccording to claim 7, wherein said water-soluble derivative is a silanolderivative of formula [R_(n) Si(OH)_(4-n) ]x, in which O<x≦4, the ngroups R are identical or different and represent independently hydrogenor an alkyl or aralkyl group and n is between 1 and
 3. 9. A cosmetic orpharmaceutical composition containing as active principle a combinationaccording to claim
 1. 10. The composition according to claim 9,containing from 1 to 6% by of peroxidised lipids and from 0.01 to 0.1%by weight, based on the organic silicon, of a biologically activeorganosilicon derivative and a cosmetically or pharmaceuticallyacceptable vehicle.
 11. A method of treatment of the skin, the scalp orthe hair, for fighting against the effects of ageing, for improvinghealing and tissue regeneration, for fighting against hair loss,improving hair re-growth or treating alopecia, comprising applying ontothe skin, scalp or hair an effective amount of a composition accordingto claim 9.